The jimpy mouse is a sex-linked recessive mutant characterized by a severe reduction of CNS myelin. Previous studies of the mutants have focused on the affected males but these studies have not elucidated the primary cause of the hypomyelination and the type of cell(s) directly affected by the mutation. The nervous system of the female carrier offers an excellent opportunity to identify the mutant cell and to study cellular interactions but the females have been neglected, probably because they do not exhibit abnormal behavior. We have recently demonstrated that the female is a mosaic for the jimpy gene which means that half of the cells express the mutant gene and the other half are normal. In optic nerve, large patches of both myelinated and unmyelinated tissue are present during development and persist into adulthood. In contrast, myelination in the brain is retarded but recovers in the adult. These findings indicate that the oligodendrocytes in brain compensate over time but some oligodendroglia in optic nerve are permanently prevented from myelinating. The mechanisms used boy oligodendrocytes to compensate can be tested by the morphological, immunocytochemical and biochemical methods available in our laboratories. With these tests we should be able to determine if the oligodendrocyte or another cell type is the site of mutation. Compensation by oligodendrocytes can occur by production of more oligodendrocytes which then make adequate amounts of myelin and/or by an increase in the rate of myelination by existing oligodendrocytes. Differences in the rate of cell proliferation and the types of labeled cells will be analyzed by autoradiography. The length of internodes, thickness of myelin sheaths and number of oligodendrocytes will be examined with morphometrics and immunocytochemistry. Changes in the rate of myelination between mosaic and normal mice will be determined by measuring levels of myelin basic protein and activities of enzymes involved in myelination. The information obtained about this model will increase our understanding of human diseases in which myelination is arrested. The differential expression of the mosaicism in brain and optic nerve may be exploited to analyze the conditions which permit recovery in the brain and inhibit myelination in the nerve.
